Vitreoretinal Interface Cells Correlate In Vivo With Uveitis Activity and Decrease With Anti-Inflammatory Treatment.

Purpose: To highlight the utility of en face swept-source optical coherence tomography angiography (SS-OCTA) in assessing vitreoretinal interface cells (VRICs) of patients with active uveitis and their dynamics. Methods: In this prospective, single-center study, 20 eyes from patients with active uveitis were analyzed using six 6 × 6-mm macular scans at three time points: active inflammation (baseline), clinically improving (T1), and resolved inflammation (T2). VRICs were visualized using 3-µm en face OCT slabs on the inner limiting membrane. The variation of VRIC number, density, and size over time was assessed, and VRIC measurements were compared with clinical grading. Results: At baseline, the VRIC count was significantly higher (552.5 VRICs) than that of the healthy controls (478.2 VRICs), with a density of 15.3 cells/mm2. VRIC number decreased significantly to 394.8 (P = 0.007) at T1, with a density of 10.9 cells/mm2 (P = 0.007). VRIC size reduced from 6.8 µm to 6.3 µm at T1 (P = 0.009) and remained stable at T2 (P = 0.3). Correlation coefficients between inflammatory parameters (anterior chamber cells and National Eye Institute vitreous haze), and VRIC count indicated a positive correlation at baseline (r = 0.53), weakening at T1 (r = 0.36), and becoming negative at T2 (r = -0.24). Conclusions: En face SS-OCTA revealed increased VRIC number and size in active uveitis, likely due to monocyte recruitment. Post-inflammation control, VRIC number, size, and density significantly decreased, returning to normal despite residual anterior chamber cells or vitreous haze. Translational Relevance: Visualization of VRICs by in vivo OCT opens up new opportunities for therapeutic targets.

Automated quantification of uveitic keratic precipitates by use of anterior segment optical coherence tomography.

BACKGROUND: Evaluation of ocular inflammation via common imaging modalities like optical coherence tomography (OCT) has emphasised cell visualisation, but automated detection of uveitic keratic precipitates (KPs) remains unexplored. METHODS: Anterior segment (AS)-OCT dense volumes of the corneas of patients with uveitic KPs were collected at three timepoints: with active (T0), clinically improving (T1), and resolved (T2) inflammation. At each visit, visual acuity and clinical grading of the anterior chamber cells were assessed. A bespoke algorithm was used to create an en face rendering of the KPs and to calculate their volume and a ratio of the volume of precipitates over the analysed area. The variation of AS-OCT-derived measurements over time was assessed, and compared with clinical grading. RESULTS: Twenty eyes from 20 patients (13 females, mean age 39 years) were studied. At T0, the mean volume of the corneal KPs was 0.1727 mm3 , and it significantly reduced to 0.1111 mm3 (p = 0.03) only at T2. The ratio between the volume of the KPs and the corneal area decreased from T0 (0.007) to T1 (0.006; p = 0.2) and T2 (0.004; p = 0.009). There was a statistically significant correlation between the AC cell count and the AS-OCT volume measurements of the KPs at the three time points. CONCLUSIONS: AS-OCT can image uveitic KPs and through a bespoke algorithm we were able to create an en face rendering allowing us to extrapolate their volume. We found that objective quantification of KPs correlated with inflammatory cell counts in the anterior chamber.

In Vivo Visualization of Macrophage-Like Cells in Patients with Uveitis by Use of En Face Swept Source Optical Coherence Tomography.

AIMS: To detect macrophage-like cells (MLCs) in uveitis patients and describe their characteristics compared to healthy subjects by using en face SS-OCTA. METHODS: Fifteen consecutive patients with "active" uveitis and 11 healthy participants underwent 6 macular scans of 6×6mm using SS-OCTA. The 3µm en face OCT slabs on inner limiting membrane were used to visualize the MLCs. RESULTS: In healthy subjects there was an average of 478.2±149.7 MLCs with a density of 13.28±4.16 cells/mm2. MLCs were larger in patients with "active" uveitis than in controls (891.18±69.46 µm2 vs.885±77.53 µm2). Patients with "active" anterior uveitis had a significantly reduced count and density of MLCs (172±14.68 and 4.77±0.4 cell/mm2) compared to controls, while patients with posterior uveitis had a statistically increased count (546.1±132.4) and area (909.23+/-54.97 µm2) of MLCs compared to controls. CONCLUSIONS: MLCs detected with en face SS-OCTA are increased in number and size in active posterior uveitis eyes compared to controls.

Use of optical coherence tomography angiography in the uveitis clinic.

As optical coherence tomography angiography is revolutionizing the ophthalmology world, the uveitis community is learning to understand where and how this new powerful imaging tool fits into the management of the panorama of ocular inflammations and infections. A non-invasive method of studying the retinal and choroidal vasculature, OCTA allows for the assessment of vessel density changes during active and inactive uveitis making it the natural imaging application of choice in uveitis clinical trials. However, these data and results are of limited utility to the ophthalmologists who are looking to apply OCTA in their everyday uveitis clinic. If employed strategically, OCTA can be a powerful tool for the uveitis specialist to evaluate iris involvement in viral uveitis; to assess the integrity of the vascular layers in the settings of white dot syndromes; to distinguish inflammatory choroidal neovascularization from outer retinal avascular inflammatory material; and to diagnose and follow infectious choroidal granulomas and satellite foci of chorioretinal inflammation without the need to administer dyes. The present review will analyze all the recent publications that apply OCTA in uveitis to offer the reader a guide on how to maximize the utility of this imaging modality in a clinical practice.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS WITH INDOCYANINE GREEN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: A Lesion-Based Analysis.

PURPOSE: To investigate choroidal granulomas visualized by indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in response to treatment. METHODS: Ten eyes of eight patients with tubercular, sarcoid, or Vogt-Koyanagi-Harada-associated choroidal granulomas were evaluated in this multicentric study. All patients underwent ICGA and OCTA at baseline, 1, and 3 months after treatment onset. Granulomas were identified as hypofluorescent lesions on intermediate ICGA phases. Late ICGA behavior and OCTA visualization were assessed. RESULTS: On baseline intermediate ICGA, 222 choroidal granulomas were detected. Overall, 174/222 granulomas were detected on baseline OCTA images. At 1 month, 28% of lesions were healed and 48 late ICGA hyperfluorescent lesions were identified. At 3 months, 63% of baseline lesions were healed, with 33 persistent late hyperfluorescent lesions. Optical coherence tomography angiography sensitivity was reduced at 1 and 3 months compared with baseline. Some flow-voids detected on OCTA at 1 and 3 months did not correspond to any visible lesion on ICGA. CONCLUSION: Different healing behaviors of choroidal granulomas were identified combining ICGA and OCTA analysis. Late ICGA hyper-fluorescent lesions may be the consequence of a possible fibrotic shift. Structural changes in the choroid may persist after active granulomas resolution resulting in persistent flow voids on OCTA.

An en face swept source optical coherence tomography study of the vitreous in eyes with anterior uveitis.

PURPOSE: To analyse vitreous anatomy patients with anterior uveitis (AU) using swept source optical coherence tomography (SS-OCT). METHODS: Patients with newly diagnosed AU and healthy participants were scanned using 16-mm SS-OCT B-scans and 12 × 12 mm cube centred at the fovea. Linear SS-OCT scans were evaluated to identify the premacular bursa (PB) above the macula and the Cloquet's canal above the optic disc. A dynamic evaluation of the 12 × 12 mm cube enabled en face measurement of the vertical and horizontal diameters of the PB and the presence/absence of communication between the PB and Cloquet's canal. RESULTS: One hundred and thirty-five subjects were included in the study. Forty-five patients were healthy (mean age 33.47 years). En face measurements of the horizontal and vertical PB mean diameters were 5.2 mm and 4.7 mm. In 90 subjects with AU (mean age 30.10 years), the mean horizontal and vertical diameter of the PB were significantly larger (p < 0.01). Thirty-seven eyes with AU presented with cystoid macular oedema (CME). The mean diameters of the PB in this subgroup were significantly larger (p < 0.01). In 75% of the entire cohort (51% of eyes in the control group, 87% of eyes with AU and 100% of eyes with AU and CME), a channel connecting the PB and Cloquet's canal could be identified. CONCLUSIONS: SS-OCT identification of a connecting channel between the PB and the Cloquet's canal suggests that inflammatory cytokines may drain from the anterior chamber through this system of channels, thus increasing the risk of CME.

Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi.

Importance: As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective: To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, Setting, and Participants: This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main Outcomes and Measures: Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results: Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and Relevance: In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.

CHOROIDAL GRANULOMAS VISUALIZED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the visualization of choroidal granulomas with swept-source optical coherence tomography angiography (OCTA). METHODS: Consecutive patients with granulomatous choroiditis due to tuberculosis, sarcoidosis, or Vogt-Koyanagi-Harada disease underwent baseline OCTA images using a 12 × 12-mm field of view, and the choroidal slabs were analyzed by two independent examiners who counted the oval areas of flow void. Simultaneously, indocyanine green angiography (ICGA) and enhanced-depth imaging OCT were performed to mark visible choroidal changes corresponding to granulomatous lesions. The lesion areas on OCTA and ICGA were assessed using the in-built caliper tool. RESULTS: Three hundred and one round-shaped areas of flow void on OCTA, 209 hypofluorescent round lesions on ICGA, and 42 hyporeflective choroidal lesions on enhanced-depth imaging OCT were identified in 23 eyes from 14 patients. Of the 209 ICGA granulomas, 197 (94.3%) had a corresponding round area of flow void on OCTA that was interpreted as a granuloma. One hundred and four additional round flow voids were identified on OCTA that did not correspond to any hypofluorescent lesion on ICGA. The mean area of the 197 granulomas detected with both imaging modalities was significantly larger on ICGA (mean 0.33 mm2) than that on OCTA (mean 0.28 mm2). CONCLUSION: Optical coherence tomography angiography seems to be an optimal imaging method for the visualization of choroidal granulomas.

Wide-field optical coherence tomography angiography for the detection of proliferative diabetic retinopathy.

PURPOSE: To compare the ability of wide-field optical coherence tomography angiography (WF-OCTA) to that of ultra-wide field fluorescein angiography (UWF-FA) and ultra-wide-field color fundus photography (UWF-CP) to detect retinal neovascularization (NV) in eyes with proliferative diabetic retinopathy (PDR). METHODS: In this cross-sectional study, naïve patients with active PDR underwent UWF-FA and UWF-CP using the Optos 200Tx and WF-OCTA with 12 × 12 mm fields of five visual fixations using the PLEX Elite 9000. NV was defined on OCTA when the co-registered B-scan with flow overlay of the vitreoretinal interface (VRI) segmentation showed extraretinal proliferation. Three masked readers examined the UWF-FA, UWF-CP, and WF-OCTA independently for the presence of NV. Statistical analysis was performed to compare the diagnostic accuracy of the 3 wide-field imaging modalities using OCT B-scan as the reference standard. RESULTS: In 82 eyes with PDR, neovascularization of the disc (NVD) was detected in 13 eyes by UWF-CP, 35 eyes with UWF-FA, and 37 eyes with OCTA using the VRI slab. Upon review of the 2500 OCT B-scans with superimposed flow overlay of each eye, NVD was confirmed in 37 eyes. The sensitivity and specificity of NVD detection were 35.1% and 97.8%, respectively for UWF-CP; 94.6% and 100%, respectively, for UWF-FA; and 100% and 100% for WF-OCTA. One hundred ninety-six foci of neovascularization elsewhere (NVE) were identified with the OCT B-scan with superimposed flow overlay. UWF-CP analysis was able to detect 62 foci of NVE of the 196 confirmed by B-scan (31.6% detection rate). An additional 11 foci of NVE seen on UWF-CP were not confirmed by B-Scan (15% false positive rate). There were 182 foci of NVE identified by UWF-FA (detection rate 91.3%), while WF-OCTA detected 196 retinal NVEs (detection rate 100%). The rate of false positives for both UWF-FA and WF-OCTA was low (< 2%). CONCLUSION: WF-OCTA can identify NV that is not evident in UWF-CP and represents a faster and safer alternative to UWF-FA for surveillance of PDR with comparable diagnostic accuracy.

Inner retinal toxicity due to silicone oil: a case series and review of the literature.

PURPOSE: Cases of sudden loss of central vision in eyes with silicone oil in situ and after oil removal have been described. The aim of this review is to present current data on silicone oil toxicity to the neuronal aspects of the retina as well as the Cleveland Clinic Abu Dhabi experience with this retinopathy (maculopathy). METHODS: A PubMed review using the terms "silicon oil" and/or "toxicity" and/or "ganglion cell" and/or "nerve fiber" was conducted to identify case reports, case series, and original articles presenting toxicity from silicon oil. Timing of visual loss, as well as SD-OCT data and RNFL/GCC analysis, was collected. Selected cases were pooled from Cleveland Clinic Abu Dhabi Vitreoretinal database to further reinforce the findings. RESULTS: Twenty-four papers were identified (case/series/articles). The earliest papers that met our criteria seemed to report vision loss at the time of or after silicone oil removal; however, more recent studies have described such toxicity from 1 to 6 months after tamponade with silicone oil in situ. Since the first description of central visual loss from silicone oil, all researchers describe a thinning of perifoveal ganglion cells measured with SD-OCT, while there is no concordance as far as RNFL changes, with some authors describing a thinning and others a thickening, but neither was ever clearly associated with visual loss. The correlation between SD-OCT hyperreflective goblets in the inner retina and histological description of intraretinal oil droplets migration seems to suggest instances of silicone oil penetration in the retinal layers. CONCLUSION: In a small percentage of cases who underwent retinal tamponade with silicone oil, ganglion cells can suffer a direct damage either from particles of oil that migrate in the retina or from direct contact with it. Indirect damage may be caused by phototoxicity due to the transparent nature of silicon oil or by inflammatory damage from cytokines sandwiched between oil and retina.

Optical coherence tomography angiography findings in systemic lupus erythematosus patients with no ocular disease.

PURPOSE: Retinal manifestations are present in 10% of patients with systemic lupus erythematosus (SLE) and consist of vascular changes that can be sight-threatening. Optical coherence tomography angiography (OCTA) is a novel imaging modality that detects movement inside the blood vessels without dye injection and transforms this movement into an angiographic map. The aim of this study is to describe subclinical vessels changes in the eyes of patients with SLE but no retinal manifestations. METHODS: In this cross-sectional study, 15 patients with SLE but no clinical ophthalmic manifestations were scanned through OCTA of the iris and at the level of the macula. Qualitative aspects of the iris vessels, and measure of the foveal avascular zone (FAZ) and vessel density were compared to a cohort of 15 normal controls. RESULTS: Patients with SLE, even in the absence of ophthalmic manifestations, present a qualitative increase in the iris vessels flow, and enlargement of the FAZ (0.22 ± 0.12 mm2) and a decrease in the vascular density (11.221 ± 1.933 mm-1) of the superficial capillary plexus on OCTA that cannot be highlighted clinically. DISCUSSION: OCTA can be used in a noninvasive way to detect subclinical vascular changes in patients with SLE. How this information will influence the follow-up and management of these cases will require further prospective studies with a collaborative effort between ophthalmologists and rheumatologists.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial - CORRIGENDUM.

This notice describes a correction to the above mentioned paper.

Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial.

BackgroundKetamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs).AimsTo establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic.MethodDouble-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760)ResultsNo significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course.ConclusionsKetamine as an anaesthetic does not enhance the efficacy of ECT.

Reduced detection of positive expressions in major depression.

In patients with depression, negative biases have been reported in various cognitive domains, but few studies have examined whether even detection is affected, i.e. are depressed patients more likely to detect the presence of negative stimuli? This study compared detection of sad and happy faces in patients (n=17) and healthy participants (n=18) using an attentional blink task. Patients with depression detected significantly fewer happy faces than matched healthy participants, but for sad faces the group difference was non-significant. The results suggest that depression may affect the detection of positive stimuli.

Psychometric properties of the Quick Inventory of Depressive Symptomatology (QIDS-SR) in UK primary care.

It is widely believed that severity of depressive disorder should guide treatment selection and many guidelines emphasise this factor. The Quick Inventory of Depressive Symptomatology (QID-SR16) is a self-complete measure of depression severity which includes all DSM-IV criterion symptoms for major depressive disorder. The object of this study was to assess the psychometric properties of the QIDS-SR16 in a primary care sample. Adult primary care patients completed the QIDS-SR16 and were assessed by a psychiatrist (blind to QIDS-SR16) with the 17-item Hamilton Rating Scale for Depression (GRID-HAMD). Internal consistency, homogeneity and convergent and discriminant validity of the QIDS-SR16 were assessed. Severity cut-off scores for QIDS-SR16 were assessed for convergence with HRSD-17 cut-offs. Published methods for converting scores to HRSD-17 were also assessed. Two hundred and eighty-six patients participated: mean age = 49.5 (s.d. = 13.8), 68% female, mean HRSD-17 = 12.6 (s.d. = 7.6). The QIDS-SR16 exhibited acceptable internal consistency (Cronbach's alpha = 0.86), a robust factor structure indicating one underlying dimension and correlated highly with the HRSD-17 (r = 0.79) but differed significantly in how it categorised the severity of depression relative to the HRSD-17 (Wilcoxon Signed Rank Test p < 0.001). Using published methods to convert QIDS-SR16 scores to HRSD-17 scores did not result in alignment of severity categorisation. In conclusion, psychometric properties of the QIDS-SR16 were found to be strong in terms of internal consistency, factor structure and convergent and discriminant validity. Using conventional scoring and conversion methods the scale was found not to concur with the HRSD-17 in categorising the severity of depressive symptoms.

Measuring depression severity in general practice: discriminatory performance of the PHQ-9, HADS-D, and BDI-II.

BACKGROUND: The UK Quality and Outcomes Framework (QOF) rewards practices for measuring symptom severity in patients with depression, but the endorsed scales have not been comprehensively validated for this purpose. AIM: To assess the discriminatory performance of the QOF depression severity measures. DESIGN AND SETTING: Psychometric assessment in nine Scottish general practices. METHOD: Adult primary care patients diagnosed with depression were invited to participate. The HADS-D, PHQ-9, and BDI-II were assessed against the HRSD-17 interview. Discriminatory performance was determined relative to the HRSD-17 cut-offs for symptoms of at least moderate severity, as per criteria set by the American Psychiatric Association (APA) and NICE. Receiver operating characteristic curves were plotted and area under the curve (AUC), sensitivity, specificity, and likelihood ratios (LRs) calculated. RESULTS: A total of 267 were recruited per protocol, mean age = 49.8 years (standard deviation [SD] = 14.1), 70% female, mean HRSD-17=12.6 (SD = 7.62, range = 0-34). For APA criteria, AUCs were: HADS-D = 0.84; PHQ-9 = 0.90; and BDI-II = 0.86. Optimal sensitivity and specificity were reached where HADS-D ≥9 (74%, 76%); PHQ-9 ≥12 (77%, 79%), and BDI-II ≥23 (74%, 75%). For NICE criteria: HADS-D AUC = 0.89; PHQ-9 AUC = 0.93; and BDI-II AUC = 0.90. Optimal sensitivity and specificity were reached where HADS-D ≥10 (82%, 75%), PHQ-9 ≥15 (89%, 83%), and BDI-II ≥28 (83%, 80%). LRs did not provide evidence of sufficient accuracy for clinical use. CONCLUSION: As selecting treatment according to depression severity is informed by an evidence base derived from trials using HRSD-17, and none of the measures tested aligned adequately with that tool, they are inappropriate for use.